The Impact of the Microbiome on Immunity to Vaccination in Humans

Abstract

Vaccines are the most effective means available for preventing infectious diseases. However, vaccine-induced immune responses are highly variable between individuals and between populations in different regions of the world. Understanding the basis of this variation is, thus, of fundamental importance to human health. Although the factors that are associated with intra- and inter-population variation in vaccine responses are manifold, emerging evidence points to a key role for the gut microbiome in controlling immune responses to vaccination. Much of this evidence comes from studies in mice, and causal evidence for the impact of the microbiome on human immunity is sparse. However, recent studies on vaccination in subjects treated with broad-spectrum antibiotics have provided causal evidence and mechanistic insights into how the microbiota controls immune responses in humans.

Keywords: human immunology; microbiome; systems vaccinology; vaccines.

Figure 1

The Microbiota Exerts Local and Global Immune Influence Through a Variety of Mechanisms (A) The microbiota can influence host responses locally at the site, such as the airways, skin, and intestines, or act at a distance and exert profound influences systemically in, for example, lymph nodes, bone marrow, or the circulation. (B) The microbiota can influence immune reactions in distal locations in several ways. Model 1 depicts systemic translocation of bacterial products such as LPS from mucosal sites. Model 2 depicts a “domino effect” mechanism, where signals from the microbiota are delivered to cells in the vicinity, which then circulate throughout the body and relay this information. Model 3 describes the effects of microbiota on distant locations via secretion of microbiota-derived metabolites. HSCs, hematopoietic stem cells. PAMPs, pathogen-associated molecular patterns.

Figure 2

Antibiotics Impair the Vaccine Response in Healthy Adults (A) Outline of the study by Hagan et al. 11 subjects were treated with antibiotics for 5 days and vaccinated with the trivalent influenza vaccine on the fourth day. These were then compared with 11 vaccinated controls untreated with antibiotics. Fecal and blood samples were collected at regular intervals. (B) Results from the study by Hagan et al. Administration of antibiotics led to reduced microbial diversity and abundance and a consequential reduction in secondary bile acids. This in turn led to increased inflammation and a diminished vaccine response. TIV, trivalent influenza vaccine; LCA, litocholic acid.

Figure 3

Unique Environmental Factors and Biological Changes in the Very Young and the Very Old that Can Be Detrimental to Vaccine Efficacy Newborn children and elderly people undergo physiological changes and are exposed to environmental stimuli that can be detrimental to their immune system. Simultaneously, they often experience decreased microbial diversity. These factors interplay to make them less responsive to vaccination.